Field of the Invention
The present invention relates to automated sample preparation and, more particularly, to an automated device and associated method for preparing cytological samples for analysis.
Description of Related Art
Immunochemistry involves the study of reactions and components of the immune system for the purpose of further diagnosing conditions that may be occurring in a subject. Cytology is a branch of biology dealing with the microscopic study of cells for purposes of medically diagnosing any abnormality, malignancy, or disease in a subject from where a specimen has been taken. Cytological techniques have achieved some acceptance at least partially because the collection of cell samples for subsequent analysis may generally be less invasive than other surgical pathological procedures, such as biopsies. For example, the cell samples used for cytological analysis can be obtained by scraping or swabbing an area of interest. Cell samples may also be obtained from an appropriate area of interest in the body of a subject by using a needle to aspirate bodily fluids from a subject. Additionally, histology is involves the study of tissue to support further medical diagnosis.
The purpose of preparing a sample, in particular a cytological sample, is to extract a desired component from the specimen so that an analysis can be performed. For example, whole blood comprises a variety of immiscible components such as red cells, white cells, platelets, etc. Often the analysis must be performed on the plasma. Further, once the desired component is isolated, it must be placed in a form suitable for subsequent analysis. In some instances, the extracted portion itself may require additional processing to render it capable of being analyzed, depending, for example, on the type of analysis to be performed. Conventional preprocessing techniques may include, for example, staining, a monolayer preparation process for preventing deformations of red blood cells, and a process for the homogeneous distribution of dry particles on a specimen slide in a unilayered, planar distribution.
Cells or tissues that have been collected from a subject may be appropriately prepared on an assay device, on which an analysis is more readily conducted and any apparent condition/pathology possibly diagnosed. Microscope slides such as, for example, deep-well slides, may be used as assay devices. Generally, it may be desirable that the cell or tissue sample be applied to and disposed substantially evenly and consistently across the surface of the assay device, particularly in a thin monolayer of cells, where the analysis (i.e., visual examination) is to be performed. However, it may be difficult to assess cell and tissue preparations (samples) on an assay device by visual examination where such preparations have not been subjected to certain further treatment. For example, lack of contrast between the individual cells or between the individual parts of cells may obscure a visual examination of the sample. In order to improve the contrast, the cell or tissue specimen applied to the assay device may be further treated with reagents in a staining process. Staining reagents are specifically chosen, depending upon the types of cells or tissues being examined, such that their absorbance is distinctively different across the various structures that are or could be present in the specimen. Staining improves the contrast between the different cell structures allowing for improved diagnosis based on a visual examination thereof.
Preparation of clinical cytological specimens in an assay for subsequent analysis requires a sequence of steps that can be exceedingly time consuming if practiced manually. Immunocytochemistry, for example, is a particular type of cytological assay preparation where protein markers are used to detect particular chemical components of cells. In immunocytochemistry, an antibody is selected such that it desirably becomes coupled to a substance of interest allowing the presence of the substance to become more readily detectable upon visual examination. Immunocytochemistry assays generally require three serial procedures. First, a sample of the specimen is disposed on an assay device, such as a slide using a cell deposition procedure. Once the sample is associated with the assay device, an epitope retrieval may be performed. Typically, epitope retrieval requires the addition of a reagent to the sample and, optionally, is followed by a heating step to raise the temperature of the sample for a prescribed amount of time. The sample may then be stained by the addition of an appropriate reagent to, and subsequent removal of any excess reagent from, the assay device (slide) being prepared. In some instances, a cover piece may be placed on the assay device in order to cover the prepared sample.
Each of the serial procedures for preparing the sample is desirably executed in a precise, consistent, repeatable and accurate manner in order to facilitate diagnosis based on the visual examination. Furthermore, emphasis on improving and economizing health care has created an increased demand on sample analysis procedures to assist with diagnosis and to provide information associated with treatment recommendations. These demands require that the sample analysis be accurate and, in many instances, be performed quickly.
As such, there exists a need for more efficient cytological sample preparation systems for improving the consistency, repeatability, and accuracy of sample preparation and analysis. In addition, manual intervention and/or manual processing in the sample preparation process may increase the likelihood that a sample will become contaminated. Any further analysis of such a contaminated sample may lead to an improper medical diagnosis. Manual intervention/manual processing may also increase the risk that the operator can become infected with any sample-borne virus or disease that may be present in the specimen. There exists a further need for more efficient cytological sample preparation systems that eliminate, reduce, or otherwise minimize, where possible, manual intervention and/or manual processing during sample preparation, such as, for example, through automation. Such a cytological sample preparation system should desirably be, for example, relatively easy to use and adaptable for processing a varying numbers of samples.